The goal of this project is to identify small molecule inhibitors of NOX2 activity as a strategy for counteracting atherosclerosis. During this period, the research team screened tens of thousands of small molecules for inhibitors of NOX2 activity. Hits were cherrypicked and validated for activity, and a set of biochemical assays and cell culture models will the further utilized to remove compounds that possess non-specific or undesirable activities. Compounds with promising activity profiles will be considered for advancement to medicinal chemistry for structure activity-guided optimization, and for further investigation in advanced models. We optimized a known NOX-2 inhibitor to improve the ADME and PK properties. The synthesized compounds currently being analyzed in collaborators hand. The collaborators are working on developing a new assay to target protein-protein interaction of the NOX-2 enzyme, a new approach.